核因子E2相关因子2表达对晚期非小细胞肺癌一线含铂化疗疗效及预后影响的研究

The role of expression of Nrf2 in predicting chemoresistance and prognosis in advanced non-small cell lung cancer receiving platinum-based rst-line chemotherapy

目的:通过检测核因子E2相关因子2(nuclear factor erythroid-2-related factor2,Nrf2)在晚期非小细胞肺癌中的表达情况,探讨其与一线含铂化疗方案疗效和患者预后的相关性。方法:回顾性分析接受一线含铂方案化疗的50例晚期非小细胞肺癌患者的临床资料,并采用免疫组织化学法检测所有患者组织标本中Nrf2的表达情况。应用SPSS17.0软件进行统计,分析Nrf2表达与一线含铂化疗方案的疗效与患者预后的相关性。结果:在晚期非小细胞肺癌患者中Nrf2的表达存在个体差异,总阳性率为34%(17/50);其中年龄≥70岁患者Nrf2的阳性率为58.3%(7/12),明显高于<70岁患者的26.3%(10/38)(P=0.041);发生远处转移患者中Nrf2阳性率为46.7%(14/30),明显高于无远处转移患者的15.0%(3/20)(P=0.021);Pearson相关分析表明,Nrf2表达与患者的年龄(r=0.370,P=0.020)、远处转移(r=0.289,P=0.042)、化疗疗效(r=0.315,P=0.026)、无进展生存期(progression free survival,PFS)(r=-0.393,P=0.006)及总生存期(overall survival,OS)(r=-0.309,P=0.029)均有相关性。COX多因素分析结果表明,Nrf2表达是一线含铂化疗方案疗效和PFS的独立预测因素(P<0.05)。结论:晚期非小细胞肺癌患者中Nrf2的表达是预测含铂方案疗效和PFS的独立预测因素,其有望成为临床上选择治疗非小细胞肺癌化疗方案的理想标志物。

Objective： To examine the expression of Nrf2 （nuclear factor erythroid 2-related factor 2） protein in patients with NSCLC （advanced non-small cell lung cancer）, and to elucidate the correlation of the expression level of Nrf2 with response to platinum-based first-line chemotherapy and the prognosis of NSCLC patients. Methods： This retrospective study enrolled 50 patients with chemotherapy-na？ve advanced NSCLC. All patients received platinum-based regimens as first-line chemotherapy. The expression level of Nrf2 protein in tumor specimens was detected by immunohistochemical analysis. The associations between Nrf2 expression with response to chemotherapy and the prognosis were analyzed by SPSS 17.0 statistical software. Results： The Nrf2 protein expression level in NSCLC patients exhibited interindividual differences and the positive rate was 34% （17/50）. The positive-expression rate of Nrf2 was higher in patients with age ≥ 70 years （58.3%, 7/12） than that in patients with age 〈 70 years （26.3%, 10/38） （P = 0.041）, which was also higher in patients with distant metastasis （46.7%, 14/30） than that in patients without metastasis （15.0%, 3/20） （P = 0.021）. The expression of Nrf2 was correlated with age （r = 0.370, P = 0.020）, distant metastasis （r = 0.289, P = 0.042）, response to platinum-based chemotherapy （r = 0.315 P = 0.026）, progression-free survival （r = –0.393, P = 0.006） and overall survival （r = –0.309, P = 0.029）. Furthermore, the expression of Nrf2 was an independent predictive factor for response to platinum-based first-line chemotherapy and progression-free survival （P 〈 0.05）. Conclusion：Nrf2 expression is an independent predictor of response to platinum-based first-line chemotherapy and the prognosis of patients with advanced NSCLC, and it may be helpful to select the appropriate chemotherapy regimen for advanced NSCLC.